1. Field of the Invention
The present invention relates to medical devices, and more specifically, to an apparatus and method for transdermal delivery of pharmaceuticals.
2. Description of the Related Art
Common methods for administering therapeutic molecules to treat illnesses or injuries to a patient include the use of hypodermic needles and oral ingestion. These methods have limitations. Delivery by oral ingestion or injection by hypodermic syringe can cause drug concentrations in the body to fluctuate between high and low values, whereas a sustained or continuous delivery is desirable. Hypodermic needle delivery is very unpopular with patients, who are often reluctant to perform this procedure on themselves. Furthermore, safe handling and disposal of the biohazardous hypodermic needles is difficult.
Oral administration of drugs remains the most common method of drug delivery because the cells lining the intestine tend to be quite permeable and because oral ingestion is generally accepted by patients. This approach, however, has a variety of shortcomings including degradation of the agent within the digestive system, local gastrointestinal irritation, and noncompliance when patients do not take their prescription in a timely manner. Furthermore, some of the drugs resulting from advances in biotechnology are protein based and cannot be taken orally or they will be digested in the gastrointestinal tract. These difficulties have spurred research into new ways to deliver therapeutic molecules, preferably by non-invasive or semi-invasive paths. Examples include jet injectors, inhalers, and external micropumps. Unfortunately, there are problems associated with the few commercially available non-invasive or semi-invasive delivery devices.
One non-invasive method of administering drugs being widely studied is the transcutaneous delivery method. The transport of various agents such as metabolites, drugs and nutrients across tissues is a function primarily of three factors: tissue permeability, the presence or absence of a driving force and the size of the area through which transport occurs. The lack of inherent permeability for many tissues renders it difficult to move agents across a body surface. The permeability of many tissues is low because cell membranes are generally composed of lipid bilayers that are relatively impermeable to ionized and uncharged polar species. For example, transport of agents across the skin has proven difficult in part because the outer layer of skin, termed the stratum corneum, consists of tightly packed cells with intercellular lipids that severely impede the passage of substances through this barrier.
Medicated adhesive patches provide one method for the transcutaneous administration of drugs. The drug is pre-loaded and steadily diffuses from the patch through the skin to blood capillaries in the skin's deeper layers. Drug patches are popular for several reasons: 1) they allow sustained drug delivery, avoiding the concentration peaks and valleys of conventional methods, 2) patients are less likely to forget, 3) the drugs are delivered painlessly, and 4) degradation of the drug by the GI tract is not an issue. Today transdermal patches delivery estrogen for hormone replacement therapy, nitroglycerine for angina, scopolamine for motion sickness and seasickness, fentanyl for pain control, clonidine for hypertension, and recently ethinylestradiol plus norelgestromin for contraception.
Despite these advantages, wearable patches are constrained by the fact that very few drugs can be formulated for transdermal delivery. The limitation comes from the highly resistive outer-most layer of the skin, the stratum corneum. Drugs delivered transdermally must be small enough to diffuse through the lipophillic gaps between the skin cells and through the skin pores. For this passive delivery, drugs must have a large therapeutic window; they must not be toxic at high concentrations yet still potent at low concentrations. Unfortunately, very few drugs meet this requirement. The benefits of wearable patches will not be realized unless methods to enhance drug passage through the stratum corneum are developed.
Iontophoresis is an alternative approach that can be utilized to deliver agents across a tissue by the application of an electrical current. In practice, iontophoretic methods generally provide positioning an electrode having a reservoir or absorbent pad that contains the agent to be transferred onto the tissue through which delivery is to occur. Another electrode that typically does not include the agent but contains, or is coated with, a conductive gel is also placed in contact with the tissue to complete the electrical circuit.
Application of a voltage between the two electrodes and across the tissue generates a current that causes the ionized agent to move towards the electrode of opposite charge, thereby driving the agent through the tissue. Neutral agents can also be transported, albeit less effectively than ionized agents, via electroosmosis. Iontophoresis also may induce the formation and/or enlargement of pores within tissues, which in turn increases tissue permeability to ionic and polar agents and drives these agents through the enlarged pores. When the tissue is skin, the agent penetrates the stratum corneum and then passes through the other layers of the epidermis into the dermis layer, the second major layer of skin. The innermost portion of the dermis is typically referred to as the papillary layer and contains a network of capillaries from the vascular system. This network absorbs the therapeutic agent and subsequently moves it to the main portion of the circulatory system. A problem associated with drug administration using iontophoresis is that it is applicable only to drugs that have an electrical charge.
While iontophoresis typically utilizes a DC power source to provide a DC current, AC current may also be used for iontophoresis. For example, U.S. Pat. No. 6,512,950 issued to Li, et al., and hereby fully incorporated by reference, discloses a variety of methods for transporting agents across tissue. The disclosed methods utilize an AC signal to maintain a substantially constant electrical state in a region of the tissue through which transport occurs, thereby allowing the agent to be transported across the issue in a controlled and predictable manner.
Another method found to be useful for increasing the transdermal passage of therapeutic agents has been to perforate the stratum corneum with microprojections. Perforating the stratum corneum with an array of microprojections that have very sharp tips, typically having a diameter of between about 1μ and about 2 μm, significantly reduces the current required for iontophoresis. U.S. Pat. No. 6,379,324 issued to Gartstein and herein incorporated by reference in its entirety, discloses a microneedle array constructed of silicon and silicon dioxide compounds that may be used to perforate the stratum corneum of the skin to deliver drugs into the epidermis through the application of iontophoresis.
There is a need to provide caregivers and their patients with procedures and devices that may be used to administer metabolites, drugs and nutrients in a painless manner at controlled and consistent rates by means that avoid the digestive tract where the drugs or metabolites may be destroyed through the digestive process. It would be advantageous for these procedures and devices to perform automatically without patient intervention so that a controlled and constant level of therapeutic agent could be delivered to the patient.